Multidrug‐resistant Gram‐negative bacterial infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug‐resistant (MDR) Gram‐negative bacilli in the pre‐ and post‐transplant period. MDR Gram‐negative bacilli, including carbapenem‐resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem‐resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram‐negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram‐negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram‐negative pathogens, especially in the setting of organ transplantation.     

BK polyomavirus in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

The present AST‐IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non‐kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV‐DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV‐DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV‐associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy‐proven BKPyV‐associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV‐DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine‐A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV‐DNAemia is definitively cleared, independent of failed allograft nephrectomy.     

Ventricular assist device‐related infections and solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

The Infectious Diseases Community of Practice of the American Society of Transplantation has published evidenced‐based guidelines on the prevention and management of infectious complications in SOT recipients since 2004. This updated guideline reviews the epidemiology of ventricular assist device (VAD) infections and provides recommendations for the management and prevention of these infections. Almost one half of those awaiting heart transplantation are supported with VADs. Despite advances in device technologies, VAD infections commonly complicate mechanical circulatory support and remain typified by common components and anatomic locations. These infections have important implications for transplant candidates, most notably increased wait‐list mortality. Strategic management of these infections is crucial for successful transplantation. Coincidentally, explantation of all VAD components at the time of transplantation is often the definitive cure for the device‐associated infection. Highlighted in this updated guideline is the reported success of transplantation in patients with a variety of pre‐existing VAD infections and guidance on post‐transplant management strategies.     

Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the AST Infectious Diseases Community of Practice review the diagnosis and management of pneumonia in the post‐transplant period. Clinical presentations and differential diagnosis for pneumonia in the solid organ transplant recipient are reviewed. A two‐tier approach is proposed based on the net state of immunosuppression and the severity of presentation. With a lower risk of opportunistic, hospital‐acquired, or exposure‐specific pathogens and a non‐severe presentation, empirical therapy may be initiated under close clinical observation. In all other patients, or those not responding to the initial therapy, a more aggressive diagnostic approach including sampling of tissue for microbiological and pathological testing is warranted. Given the broad range of potential pathogens, a microbiological diagnosis is often key for optimal care. Given the limited literature comparatively evaluating diagnostic approaches to pneumonia in the solid organ transplant recipient, much of the proposed diagnostic algorithm reflects clinical experience rather than evidence‐based data. It should serve as a template which may be modified according to local needs. The same holds true for the suggested empiric therapies, which need to be adapted to the local resistance patterns. Further study is needed to comparatively evaluate diagnostic and empiric treatment strategies in SOT recipients.     

Cryptococcosis in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of cryptococcosis in the pre‐ and post‐transplant period. The current update now includes a discussion of cryptococcosis, which is the third most common invasive fungal infection in SOT recipients. Infection often occurs a year after transplantation; however, early infections occur and donor‐derived infections have been described within 3 months after transplant. There are two main species that cause infection, Cryptococcus neoformans and C gattii. Clinical onset may be insidious, but headaches, fevers, and mental status changes should warrant diagnostic testing. The lateral flow cryptococcal antigen assay is now the preferred test from serum and cerebrospinal fluid due to its rapidity, accuracy, and cost. A lumbar puncture with measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Lipid amphotericin B plus 5‐flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate‐to‐severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild‐to‐moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.     

Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of adenovirus infections after solid organ transplantation. Adenovirus is an important cause of infectious complications in both stem cell transplant and SOT patients, causing a range of clinical syndromes including pneumonitis, colitis, and disseminated disease. The current update of the guidelines highlights that adenovirus surveillance testing should not be performed in asymptomatic recipients. Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient. The initial and most important components of therapy remain supportive care and decrease in immunosuppression. The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers. Intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia. Future approaches to treatment of adenovirus disease may include administration of adenovirus‐specific T‐cell therapy.     

Strategies for safe living following solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

The present AST‐IDCOP guidelines update information on strategies for safe living after organ transplantation. While transplantation carries an increased risk for infection from the recipient's environment due to lifelong immunosuppression, the goal is for the recipient to be able to return to their home and live as normal a life as possible with a functioning graft. The current guideline provides updates to prior recommendations including additions on infections from water and food sources, exposures to animals, cannabis use as well as sexual exposures or those encountered with travel. Similar to the prior editions, many of the recommendations are based on good infection prevention standards, extrapolation from other immunocompromised hosts, and risks found from cases series in transplant patients. Enhanced education and attention to incorporating safe living strategies into daily life should help to accomplish successful transplant with recipients achieving a fulfilling life away from the hospital.     

Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre‐ and post‐transplant period. A majority of transplant recipients are seropositive for HSV‐1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir‐resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV‐specific prophylaxis should be considered for all HSV‐1 and HSV‐2–seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.     

Vancomycin‐resistant Enterococcus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation address vancomycin‐resistant enterococci (VRE) infections in SOT candidates and recipients. VRE are an important cause of infection and have been named by the CDC as a serious public threat. Typically, a commensal of the gastrointestinal tract, VRE may become pathogenic after abdominal organ manipulation like transplantation. This guideline reviews the microbiology, antimicrobial resistance mechanisms, epidemiology, and clinical manifestations of VRE infection in the context of solid organ transplantation. Treatment regimens including combination therapies and novel investigational agents are also reviewed. Finally, an updated appraisal of infection control measures relevant to VRE infection and colonization is presented.     

Screening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

This updated section of the guideline from the Infectious Diseases Community of Practice of the American Society of Transplantation reviews the screening of donor and candidate prior to solid organ transplantation. Screening of donor and candidate is vital for optimizing post‐transplant outcomes. Risk assessment based on detailed history and appropriate diagnostic evaluation is essential. Serologic screening for certain viral infections is important and aids in immunization counseling and risk mitigation of recipients. In addition to serology, nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus has been required for deceased and living donors. Certain endemic exposure may warrant additional evaluation beyond recommended standard testing. Diagnosed infection in the donor or recipient warrants treatment as well as additional testing and/or prophylaxis to mitigate risk for post‐transplant complications. Certain infections in the immediate pre‐transplant period may warrant delay of transplantation.     

Travel medicine,transplant tourism,and the solid organ transplant recipient—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review recommendations for prevention and management of travel‐related infection in solid organ transplant (SOT) recipients as well as risks associated with transplant tourism. Counseling regarding travel post‐transplant should be included during the pre‐transplant evaluation, and all SOT recipients should be seen by a travel medicine specialist prior to traveling to destinations with higher rates of infection. Patients should be advised on vaccine‐preventable illnesses as well as any need for prophylaxis (ie, malaria) based on their individual travel itineraries. Information with regards to specific recommendations for vaccines and prophylactic medications, along with drug‐drug interactions, is summarized. Counseling should be provided for modifiable risks and exposures (ie, food and water safety, and insect bite prevention) as well as non‐infectious travel topics. These guidelines also briefly address risks associated with transplant tourism and specific infections to consider if patients seek care for transplants done in foreign countries.     

Cytomegalovirus in solid organ transplant recipients—Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice

Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence‐based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug‐resistant CMV infection are presented. There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.     

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre‐ and post‐transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter‐associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species‐level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long‐term multidrug regimens, and consideration of complex drug‐drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.     

Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post‐operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%‐53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end‐stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug‐resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri‐operative antibiotic prophylaxis to minimize post‐operative SSIs.     

Intra‐abdominal infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

This new guideline from the AST IDCOP reviews intra‐abdominal infections (IAIs), which cause substantial morbidity and mortality among abdominal SOT recipients. Each transplant type carries unique risks for IAI, though peritonitis occurs in all abdominal transplant recipients. Biliary infections, bilomas, and intra‐abdominal and intrahepatic abscesses are common after liver transplantation and are associated with the type of biliary anastomosis, the presence of vascular thrombosis or ischemia, and biliary leaks or strictures. IAIs after kidney transplantation include renal and perinephric abscesses and graft‐site candidiasis, which is uncommon but may require allograft nephrectomy. Among pancreas transplant recipients, duodenal anastomotic leaks can have catastrophic consequences, and polymicrobial abscesses can lead to graft loss and death. Intestinal transplant recipients are at the highest risk for sepsis, infection due to multidrug‐resistant organisms, and death from IAI, as the transplanted intestine is a contaminated, highly immunological, pathogen‐rich organ. Source control and antibiotics are the cornerstone of the management of IAIs. Empiric antimicrobial regimens should be tailored to local susceptibility patterns and pathogens with which the patient is known to be colonized, with subsequent optimization once the results of cultures are reported.     

Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim‐sulfamethoxazole (TMP‐SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO₂ < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β‐d ‐glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP‐SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6‐12 months post–transplant, preferably with TMP‐SMX.     

Varicella zoster virus in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, prevention, and management of varicella zoster virus (VZV) in the pre‐ and post‐transplant period. Primary varicella is an uncommon complication post‐solid‐organ transplant (SOT), except among pediatric transplant patients and those seronegative for VZV. As the majority of SOT recipients are seropositive for VZV, herpes zoster (HZ) occurs frequently following SOT, particularly among recipients who are older (≥65 years of age) and those receiving more intensive immunosuppression. Transplant providers should aware of the increased risk for HZ‐related complications such as dissemination, organ‐specific involvement, and post‐herpetic neuralgia. Treatment for localized zoster is primarily given as oral regimens, but those with more complicated presentations or those at risk for dissemination should be treated initially with IV therapy. Available antiviral prophylaxis regimens and vaccination strategies for varicella and HZ among these immunosuppressed patients remain a mainstay for prevention in the pre‐and post‐transplant periods. Finally, we discuss important approaches to addressing post‐exposure prophylaxis and infection control practices for those SOT patients with documented VZV infections.     

Nocardia infections in solid organ transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter‐ and intraspecies susceptibility patterns can vary. Sulfonamide is the first‐line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.     

Endemic fungal infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre‐ and post‐transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen‐based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step‐down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug‐drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.     

Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of urinary tract infections (UTI) in solid organ transplantation, focusing on kidney transplant (KT) recipients. KT recipients have unique risk factors for UTI, including indwelling stents and surgical manipulation of the genitourinary tract. KT recipients experience multi‐drug antibiotic‐resistant infections—UTI prevention and management strategies must consider risks of antimicrobial resistance. Non‐antimicrobial prevention strategies for UTI in KT recipients are reviewed. It is important to recognize that some renal transplant recipients with UTI may primarily present with fever, malaise, leukocytosis, or a non‐specific sepsis syndrome without symptoms localized to the urinary tract. However, asymptomatic bacteriuria (AB) must be distinguished from UTI because AB is not necessarily a disease state. Accumulating data indicate that there are no benefits of antibiotics for treatment of AB in KT recipients more than 2 months after post‐transplant. Further research is needed on management of AB in the early (<2 months) post‐transplant period, prophylaxis for UTI in this era of antibiotic resistance, recurrent UTI, non‐antimicrobial prevention of UTI, and uropathogens identified in donor urine and/or preservative fluid cultures.